Therapeutic Effect of Repeated Natural Killer T Cell Stimulation in Mouse Cholangitis Complicated by Colitis

• DOI: 10.1007/s10620-005-2949-2
• Publication Date: 2005-09-26T07:59:42Z
• Authors: Yoshihiro Numata; Susuma Tazuma; Yoshitaka Ueno; Tomoji Nishioka; Hideyuki Hyogo; Kazuaki Chayama
• Keywords: Transplant surgery

Primary sclerosing cholangitis is often complicated by ulcerative colitis. Recently, we reported on Th1-dominant cholangitis associated with experimental colitis, and natural killer T (NKT) cells might play an important role in this model. The aim of this study was to clarify the immunopathogenic role of NKT cells in this model using alpha-galactosylceramide. CD-1 mice were administered 2.0% dextran sulfate sodium for 29 days and injection of alpha-galactosylceramide was performed every 5 days, then inflammation was assessed. Mononuclear cells from the liver were analyzed with respect to cytokine production and the surface marker. alpha-Galactosylceramide improved survival rate, weight gain, and inflammation score. Also, interferon-gamma release from MNC, CD4/CD8 ratio, NKT cell population, and NK cell population were decreased by this treatment. These findings indicate that repeated stimulation of NKT cells modifies the Th1/Th2 balance to reduce Th1 dominance, and this may be a mechanism by which alpha-galactosylceramide has a therapeutic effect.